Anti-CD38 Antibodies for Treatment of Light Chain Amyloidosis and Other CD38-Positive Hematological Malignancies

Abstract

The present invention relates to methods of treatment of light chain amyloidosis and other CD38-positive hematological malignancies with anti-CD38 antibodies.

What is claimed is: 
     
         1 . A method of treating light chain amyloidosis (AL) in a newly diagnosed AL patient, comprising administering to the patient a pharmaceutical composition comprising an anti-CD38 antibody and a hyaluronidase for a time sufficient to treat the AL, wherein:
 a) the anti-CD38 antibody is of an IgG1 isotype comprising a heavy chain variable region (VH) sequence of SEQ ID NO: 4 and a light chain variable region (VL) sequence of SEQ ID NO: 5; and   b) the pharmaceutical composition is administered in combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD).   
     
     
         2 . The method of  claim 1 , wherein the anti-CD38 antibody and CyBorD are administered simultaneously. 
     
     
         3 . The method of  claim 1 , wherein the anti-CD38 antibody and CyBorD are administered sequentially or separately. 
     
     
         4 . The method of  claim 1 , wherein the cyclophosphamide, the bortezomib and the dexamethasone are administered simultaneously. 
     
     
         5 . The method of  claim 1 , wherein the cyclophosphamide, the bortezomib and the dexamethasone are administered sequentially or separately. 
     
     
         6 . The method of  claim 1 , wherein the patient is undergoing hematopoietic stem cell transplantation (HSCT). 
     
     
         7 . The method of  claim 6 , wherein the HSCT is allogeneic. 
     
     
         8 . The method of  claim 6 , wherein the HSCT is autologous or syngeneic. 
     
     
         9 . The method of  claim 6 , wherein the HSCT comprises transplantation of blood stem cells derived from bone marrow, blood or amniotic fluid. 
     
     
         10 . The method of  claim 6 , wherein the anti-CD38 antibody is administered prior to HSCT. 
     
     
         11 . The method of  claim 6 , wherein the anti-CD38 antibody is administered during or after HSCT. 
     
     
         12 . The method of  claim 6 , wherein the patient has completed chemotherapy and/or radiation therapy prior to HSCT. 
     
     
         13 . The method of  claim 1 , wherein the patient is further treated with radiotherapy. 
     
     
         14 . The method of  claim 1 , wherein the anti-CD38 antibody does not mediate killing of CD34-positive hematopoietic progenitor cells by complement dependent cytotoxicity (CDC). 
     
     
         15 . The method of  claim 1 , wherein the anti-CD38 antibody induces killing of CD38 positive plasma cells by antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement dependent cytotoxicity (CDC), apoptosis, or modulation of CD38 enzymatic activity. 
     
     
         16 . The method of  claim 1 , wherein the anti-CD38 antibody binds at least to the region SKRNIQFSCKNIYR (SEQ ID NO: 2) and the region EKVQTLEAWVIHGG (SEQ ID NO: 3) of human CD38 SEQ ID NO: 1. 
     
     
         17 . The method of  claim 1 , wherein the anti-CD38 antibody comprises a heavy chain comprising an amino acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to that of SEQ ID NO: 12 and a light chain comprising an amino acid sequence that is 95%, 96%, 97%, 98%, 99% or 100% identical to that of SEQ ID NO: 13. 
     
     
         18 . The method of  claim 1 , wherein the anti-CD38 antibody comprises the heavy chain of SEQ ID NO: 12 and the light chain of SEQ ID NO: 13.